Bempedoic acid and Ezetimibe

NEXLIZET, a combination of bempedoic acid and ezetimibe, is indicated: as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Bempedoic acid, a component of NEXLIZET, is indicated: to reduce the risk of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, or coronary revascularization) in adults at increased risk for these events who are unable to take recommended statin therapy (including those not taking a statin).

NEXLIZET contains bempedoic acid and ezetimibe. NEXLIZET reduces elevated LDL-C through inhibition of cholesterol synthesis in the liver and absorption in the intestine. Bempedoic acid Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors.

Administer one tablet (180 mg bempedoic acid and 10 mg ezetimibe) orally once daily with or without food. Swallow the tablet whole. Coadministration with Bile Acid Sequestrants: Administer at least 2 hours before or at least 4 hours after bile acid sequestrants.

NEXLIZET is contraindicated in patients with a prior hypersensitivity to ezetimibe or bempedoic acid or any of the excipients in NEXLIZET. Serious hypersensitivity reactions, such as anaphylaxis, angioedema, rash and urticaria have been reported with ezetimibe or bempedoic acid. Known hypersensitivity to ezetimibe or bempedoic acid or any of the excipients in NEXLIZET.

Hyperuricemia: Elevations in serum uric acid have occurred. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate. Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLIZET at the first sign of tendon rupture. Avoid NEXLIZET in patients who have a history of tendon disorders or tendon rupture.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hyperuricemia Tendon Rupture Common adverse reactions with NEXLIZET in the primary hypercholesterolemia trials (incidence ≥ 2% and more frequently than placebo) were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, elevated liver enzymes, diarrhea, arthralgia, sinusitis, fatigue, and influenza. The common adverse reaction associated with bempedoic acid in the cardiovascular outcomes trial (incidence ≥ 2% and more frequently than placebo) were hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis.

No specific pharmacokinetic drug interaction studies with NEXLIZET have been conducted. Table 4 lists drug interactions with NEXLIZET that have been identified in studies with bempedoic acid or ezetimibe. Table 4. Clinically Important Drug Interactions with NEXLIZET Simvastatin Clinical Impact: Concomitant use of NEXLIZET with simvastatin causes an increase in simvastatin concentration and may increase the risk of simvastatin-related myopathy. Intervention: Avoid concomitant use of NEXLIZET with simvastatin greater than 20 mg. Pravastatin Clinical Impact: Concomitant use of NEXLIZET with pravastatin causes an increase in pravastatin concentration and may increase the risk of pravastatin-related myopathy.

Store at 68°F to 77°F (20°C to 25°C), excursions permitted to 59°F to 86°F (15°C to 30°C). Store and dispense in the original package protected from extreme heat and humidity.